Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population
This article is protected by copyright. All rights reserved. The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherot...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
|
| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/nhmrc/334047 http://hdl.handle.net/20.500.11937/80046 |
| _version_ | 1848764148134969344 |
|---|---|
| author | Lewis, J.P. Riaz, M. Xie, S. Polekhina, G. Wolfe, R. Nelson, M. Tonkin, A.M. Reid, Christopher Murray, A.M. McNeil, J.J. Shuldiner, A.R. Lacaze, P. |
| author_facet | Lewis, J.P. Riaz, M. Xie, S. Polekhina, G. Wolfe, R. Nelson, M. Tonkin, A.M. Reid, Christopher Murray, A.M. McNeil, J.J. Shuldiner, A.R. Lacaze, P. |
| author_sort | Lewis, J.P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | This article is protected by copyright. All rights reserved.
The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post-hoc analysis of N=13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrolment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease endpoint (CVD), and composites of major adverse cardiovascular events (MACE) and ischaemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P<0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331-A and treatment group, for CVD (P=0.65), MACE (P=0.32), STROKE (P=0.56), MHEM (P=0.59) or ICB (P=0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population. |
| first_indexed | 2025-11-14T11:14:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-80046 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:14:45Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-800462021-06-24T04:19:10Z Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population Lewis, J.P. Riaz, M. Xie, S. Polekhina, G. Wolfe, R. Nelson, M. Tonkin, A.M. Reid, Christopher Murray, A.M. McNeil, J.J. Shuldiner, A.R. Lacaze, P. Genetics aspirin cardiovascular disease platelet aggregation This article is protected by copyright. All rights reserved. The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post-hoc analysis of N=13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrolment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease endpoint (CVD), and composites of major adverse cardiovascular events (MACE) and ischaemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P<0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331-A and treatment group, for CVD (P=0.65), MACE (P=0.32), STROKE (P=0.56), MHEM (P=0.59) or ICB (P=0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population. 2020 Journal Article http://hdl.handle.net/20.500.11937/80046 10.1002/cpt.1959 eng http://purl.org/au-research/grants/nhmrc/334047 http://purl.org/au-research/grants/nhmrc/1127060 fulltext |
| spellingShingle | Genetics aspirin cardiovascular disease platelet aggregation Lewis, J.P. Riaz, M. Xie, S. Polekhina, G. Wolfe, R. Nelson, M. Tonkin, A.M. Reid, Christopher Murray, A.M. McNeil, J.J. Shuldiner, A.R. Lacaze, P. Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title | Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title_full | Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title_fullStr | Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title_full_unstemmed | Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title_short | Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| title_sort | genetic variation in pear1, cardiovascular outcomes and effects of aspirin in a healthy elderly population |
| topic | Genetics aspirin cardiovascular disease platelet aggregation |
| url | http://purl.org/au-research/grants/nhmrc/334047 http://purl.org/au-research/grants/nhmrc/334047 http://hdl.handle.net/20.500.11937/80046 |